The evolution of retinoic acid signaling in animals: functional insights from a mollusc embryo

视黄酸是维生素A的一种生物活性形式，作为细胞之间的信号，对人类发育至关重要。 视黄酸信号被认为是脊椎动物的独特特征。 然而，最近在多种无脊椎动物基因组中发现了控制视黄酸信号的基因，但还不清楚视黄酸信号在这些动物中的作用。 这个项目利用了最近发现的视黄酸信号在蜗牛胚胎中的作用。 该小组发现，对维甲酸信号传导的几种不同组分的实验操作影响了发育中胚胎的相同结构，这表明这些不同组分在脊椎动物中共同作用。 该项目有望产生对脊椎动物以外的视黄酸信号传导的最全面的理解，并改变我们对这种途径如何在进化中出现的理解。该项目还将有助于培养本科生和研究生水平的科学家，推广到当地的K-12学生，并为发育生物学本科课程提供开源教学资源。（aka Ilyanassa），研究小组将首先利用初步数据中关于RA效应的知识，对另外17个推定的RA通路组分基因进行功能筛选，然后进一步测试具有预期表型的基因与已知组分的功能性相互作用。同时，他们将测量各发育阶段内源性RA异构体的水平。在第二组实验中，他们将专门测试RA中断对神经系统发育的影响，这是该途径在脊椎动物中的关键作用。在神经发生中的作用得到了其他无脊椎动物的支持，因此这将是对比较工作的重要贡献。这些实验将进一步了解RA的作用，并将这些结果与新生的比较RA文献。在最后一组实验中，他们将测试RA功能机制的几个特定模型，包括系统是否对不同配体剂量和不同转录水平作出反应。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Retinoic acid is a biologically active version of Vitamin A that acts as a signal between cells and is crucial for human development. Retinoic acid signaling was thought to be a unique characteristic of the vertebrates. Recently however, the genes that control retinoic acid signaling have been found in multiple invertebrate genomes, but it is not clear what retinoic acid signaling is doing in these animals. This project takes advantage of recently discovered roles of retinoic acid signaling in a snail embryo. This group has found that experimental manipulations of several different components of retinoic acid signaling impacted the same structures in the developing embryo, indicating that these different components are working together in a pathway as they do in vertebrates. This project is expected to generate the most comprehensive understanding of retinoic acid signaling outside of vertebrates, and change our understanding of how this pathway arose in evolution. This project will also contribute to the training of undergraduate and graduate level scientists, outreach to local K-12 students, and an open-source teaching resource for undergraduate courses in developmental biology.To characterize the components and roles of the retinoic acid (RA) pathway in the embryo of the gastropod Tritia (aka Ilyanassa), the research team will first use the knowledge of RA effects from preliminary data to carry out a functional screen of 17 additional putative RA pathway component genes, then further test genes with the expected phenotypes for functional interactions with known components. In parallel, they will measure levels of endogenous RA isomers across developmental stages. In a second set of experiments, they will specifically test the effect of RA disruption on the development of the nervous system, a key role of the pathway in vertebrates. A role in neurogenesis has some support from other invertebrates, so this will be an important contribution to that comparative work. These experiments will further the understanding of the roles of RA, and integrate these results with the nascent comparative RA literature. In a final set of experiments, they will test several specific models for the mechanisms of RA function, including whether the system responds to different ligand dosages with different transcription levels.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.